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Aims. To model the parenteral nutrition-associated liver disease (PNALD) in rat normal hepatocytes BRL and investigate the role of endoplasmic reticulum stress- (ERS-) related IRE1α signal in the process of PNALD. Methods. The BRL cells were treated with different concentrations of soybean oil emulsion (SO) to induce hepatocyte fatty degeneration. The PNALD cell disease model was further confirmed by analysis of Oil Red O staining and biochemical parameters. Next, the IRE1α was silenced by specific shRNAs via lentivirus and the role of IRE1α in anticytotoxicity and the expression level of ERS-related protein IRE1α and p-IRE1α were measured. Results. The results of Oil Red O staining indicated that the PNALD was successfully established in BRL cells and the CCK-8 data indicated which 0.6% that SO was further applied to the experiment owing to its better induction of PNALD and less toxicity to the cells. Besides, the value of biochemical parameters (TBIL, DBIL, ALT, and AST) was also elevated in the SO group compared with the NG group. After knockdown of IRE1α, the PNALD was also induced while the cells were more tolerant to SO. The less positive Oil Red O staining and reduced values of biochemical parameters were observed in the shIRE1α group when compared to the shControl, both of which accepted SO treatment. Conclusion. IRE1α was induced in PNALD cell model and suppression of IRE1α resulted in reduced steatosis in this cell disease model. Taken together, our data suggested that the IRE1α pathway may be involved in the development of PNALD.

Background. Cholestasis is a common but serious clinical condition in preterm neonates. The current management for preterm neonatal cholestasis has limitations. The aim of this study was to determine effects of Bifidobacterium supplementation on the prevention and alleviation of cholestasis in preterm infants with very low birth weight. Methods. Preterm neonates with very low birth weight were enrolled in the Children’s Hospital of Soochow University between December 2012 and December 2017. The patients were randomly assigned into Bifidobacterium and control groups, and effects of Bifidobacterium supplementation on the outcomes were compared between the two groups. Results. There was no significant difference in the baseline characteristics in the two groups. Notably, the proportion of cases with neonatal cholestasis was significantly lower, with fewer neonatal cholestasis-associated complications in the Bifidobacterium group compared with the control group (6% versus 22%, P<0.01). Furthermore, the Bifidobacterium group exhibited less severe cholestasis and better improvement of the liver function than the control group as evidenced by the biochemical tests (P<0.05). Finally, comparison of the other outcomes revealed that significant shorter duration of hospitalization (14.45±2.13 versus 16.12±2.22 days, P<0.01), fewer days to reach the full enteral feeding (9.2±2.11 versus 12±5.67 days, P<0.01), shorter duration of meconium passage (5.0±3.6 versus 6.6±3.38 days, P<0.05), lower proportion of cases on fasting and duration of fasting (0.8% versus 5.6%, P<0.05 and 3.0±1.6 versus 5.6±2.38 days, P<0.01, respectively), and shorter duration of weight gain to normal (4.77±2.49 versus 6.87±2.71 days, P<0.01) in the Bifidobacterium group versus the control group. Conclusions. Bifidobacterium supplementation has significantly preventive and other beneficial effects on the management of cholestasis in preterm infants with very low birth weight. Its long-term safety and effectiveness will need further investigation. This trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR1900022296).